The main objective of this research program is to use the MOPC-315 tumor system in BALB/c mice to enhance our understanding of the interplay between cyclophosphamide (CY) therapy and the host immune system in the cure of tumors. The timing and dose of the drug as well as the number of tumor cells transplanted and time in the mouse will be assessed in relation to the facets of the immune system which may selectively intervene either to enhance tumor growth or to act synergistically with the drug to cure the tumor. The practical application of this knowledge to human cancer would be the development of a more rational basis for drug administration in conjunction with immunotherapy for the treatment of cancer. We will use a variety of methods to assess the role of the host immune system as follows: lymphoid cells, before and after fractionation into subsets as well as before and after in vitro immunization, will be assessed for anti-tumor cytotoxicity by both in vitro and in vivo assays; humoral immunity will be assessed by measurement of antibody levels and by tests for antibody and complement dependent cytotoxicity. Specifically, the goals are: 1) To determine why a low dose CY therapy (15 mg/kg) which is effective in curing mice with 10-14 day large tumors (20-25 mm) is ineffective for mice bearing 4-day non-palpable MOPC-315 tumors; 2) To assess the relative contribution of the drug's cytotoxic effect and the host immune response when mice are cured with a high dose of CY (200 mg/kg); 3) To evaluate the kinetics of tumor regression and cellular infiltration at the tumor sites; 4) To determine whether CY therapy of large tumors increases the immunogenicity of the tumor cells and/or their susceptibility to immune lysis; 5) To evaluate the magnitude, duration, and nature (cellular and humoral) of anti-tumor immunity in mice cured of different size tumors by CY; 6) To evaluate the effect of CY therapy of mice bearing large tumors on the general immune status of the mice; 7) To determine whether our findings for the MOPC-315 system are applicable to other tumor systems; 8) To evaluate the potential usefulness of 4-hydroxycyclophosphamide (4-HP-CY) to screen tumor systems for effectiveness of CY therapy.